Our laboratories have identified a tumor- (cancer-) associated growth protein, tNOX, as a target for (-)-epigallocatechin gallate [EGCg], the principal anti-cancer tea catechin, to help explain the potential anti-cancer benefits of tea. NOX proteins are located at the cell surface and are responsible for the increase in cell size following cell division. Cells in which NOX activity is blocked are unable to enlarge in vitro. Therefore, they cease to divide and, after several days, undergo programmed cell death (apoptosis). The cancer-specific tNOX protein which is the potential tea target, differs from the non-cancer of constitutive CNOX protein primarily in its response to tNOX-targeted anti-tumor substances such as EGCg. At therapeutic doses such drugs slow the growth of cancer cells and inhibit tNOX but not that of CNOX and growth of non-cancer cells. The lack of effect on non-cancer but rapidly proliferating cells provides compelling evidence for the cancer specificity of the tNOX- response to EGCg and other tea catechins. This project is to utilize new information on synergy among polyphenols in inhibiting tNOX and tumor growth to modify the activity of EGCg through combination of tea with other botanicals enriched, for example, in anti-cancer vanilloids and epicatechins. Also research will be done to identify the determinants of anti-cancer polyphenole bioavailability to include development of appropriate methodology. Basic studies will focus on 1) the mechanisms of catechin inhibition of cancer cell growth and induction of apoptosis, 2) the mechanism of cancer specificity of EGCg and 3) the basis of anti- cancer synergy among vanilloids, epicatechin and other polyphenols. Emphasis will be on development of clinically useful polyphenol compositions with health benefits in both cancer treatments and prevention.